• Icro Meattini, Maria Carmen De Santis, Luca Visani, Marta Scorsetti, Alessandra Fozza, Bruno Meduri, Fiorenza De Rose, Elisabetta Bonzano, Agnese Prisco, Valeria Masiello, Eliana La Rocca, Ruggero Spoto, Carlotta Becherini, Gladys Blandino, Luca Moscetti, Riccardo Ray Colciago, Riccardo A Audisio, Etienne Brain, Saverio Caini, Marije Hamaker, Orit Kaidar-Person, Matteo Lambertini, Livia Marrazzo, Calogero Saieva, Tanja Spanic, Vratislav Strnad, Sally Wheelwright, PoortmansPhilip M PPMPDepartment of Radiation Oncology, Iridium Netwerk, Wilrijk-Antwerp, Belgium; Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk-Antwerp, Belgium., Lorenzo Livi, and EUROPA Trial Investigators.
• Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy; Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy. Electronic address: icro.meattini@unifi.it.
• Lancet Oncol. 2024 Dec 11.

BackgroundOptimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population.MethodsThis non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre). Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone breast-conserving surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive single-modality endocrine therapy or radiotherapy. Endocrine therapy consisted of daily oral aromatase inhibitors or tamoxifen, for a total planned duration of 5-10 years as per clinical discretion, while radiotherapy was administered as either whole breast or partial breast irradiation, delivered in 5-15 fractions. Randomisation was stratified by health status according to the Geriatric 8 (G8) screening tool and by age, with allocation concealed and no blinding. The co-primary endpoints were the change in HRQOL, assessed by the global health status (GHS) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core module at 24 months, and 5-year IBTR rates (not reported here). This preplanned interim analysis was performed once at least 152 patients completed the 24-month GHS HRQOL assessment. The safety population comprised patients who received the study intervention at least once after randomisation. The study is registered with ClinicalTrials.gov, NCT04134598, and is ongoing and actively recruiting.FindingsBetween March 4, 2021, and June 14, 2024, 731 women were randomly assigned to receive radiotherapy (n=365) or endocrine therapy (n=366). This analysis included 104 patients in the radiotherapy group and 103 in the endocrine therapy group, with a median follow-up of 23·9 months (IQR 22·9-24·2). Patients were predominantly White (204 [99%] of 207) and the median age was 75·0 years (IQR 73·0-80·0) in the radiotherapy group and 74·0 years (72·0-80·0) in the endocrine therapy group. 86 patients in the radiotherapy group and 75 in the endocrine therapy group completed the 24-month HRQOL assessment. The mean baseline GHS score was 71·9 (SD 19·1) in the radiotherapy group and 75·5 (19·3) in the endocrine therapy group. At 24 months, the age-adjusted, G8 score-adjusted mean change from baseline in GHS was -3·40 (95% CI -7·82 to 1·03; p=0·13) in the radiotherapy group and -9·79 (-14·45 to -5·13; p<0·0001) in the endocrine therapy group, with an adjusted mean difference of 6·39 (0·14 to 12·65; p=0·045) favouring radiotherapy. Treatment-related adverse events were less frequent in the radiotherapy group (65 [67%] of 97 patients) compared with the endocrine therapy group (76 [85%] of 89). The most common grade 3-4 adverse events were arthralgia (six [7%] of 89 in the endocrine therapy group vs 0 of 97 in the radiotherapy group), pelvic organ prolapse (three [3%] vs 0), fatigue, hot flashes, myalgia, bone pain, and fractures (two [2%] vs 0 for each). Serious adverse events were reported in 15 (15%) patients in the radiotherapy group and 13 (15%) in the endocrine therapy group. There were no treatment-related deaths in either group.InterpretationEndocrine therapy was associated with a greater reduction in HRQOL, as measured by GHS, compared with radiotherapy at 24 months. While these interim results suggest radiotherapy might better preserve HRQOL in older women with low-risk early breast cancer, further data on disease control outcomes and final patient accrual are needed to draw definitive conclusions.FundingFondazione Radioterapia Oncologica.Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

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